There’s new information on how two widely used biologic treatments for severe asthma affect the immune system at a cellular level. The treatments in question — mepolizumab and dupilumab — have been in use for about a decade but recently provided Swedish researchers with new insights into their mechanisms and potential for long-term disease remission.
The study, “High-Dimensional Analysis of Type 2 Lymphocyte Dynamics During Mepolizumab or Dupilumab Treatment in Severe Asthma,” was conducted by researchers at Karolinska Institutet and Karolinska University Hospital in Stockholm and published in Allergy, the European Journal of Allergy and Clinical Immunology. The objective was to determine how the biologic drugs affect circulating type 2 lymphocytes in patients with severe asthma and whether they improve patient outcomes when tapered or discontinued over time.
Researchers conducted a high-dimensional analysis of blood samples from 40 patients with severe asthma, using advanced flow cytometry and single-cell RNA sequencing. The study focused on type 2 lymphocytes, a group of immune cells known to drive inflammation in asthma. Patients received either mepolizumab or dupilumab over four and 12 months.
Key findings showed that mepolizumab significantly increased the presence of type 2 innate lymphoid cells (ILC2), type 2 T helper (Th2) and type 2 cytotoxic (Tc2) cells in the bloodstream. These cells exhibited a shift toward a less tissue-invasive phenotype, marked by reduced expression of homing receptors like CXCR4 and GPR183. Similarly, their ability to produce inflammatory cytokines in response to triggers was enhanced.
Dupilumab-treated patients also showed elevated levels of ILC2 cells, particularly those with a CD117^low signature, suggesting a similar redirection of immune activity away from the airways.
Ultimately, researchers said mepolizumab came out on top, reducing airway inflammation not just by neutralizing eosinophils but by redirecting trafficking of inflammatory type 2 lymphocytes away from airway-homing.
The research highlights a transformative understanding of how biologics modulate immune responses in asthma, with implications for personalized treatment strategies and long-term disease management. According to researchers, the findings could pave the way for biologics-free remission in some patients.
